Objective. A comparative evaluation of the efficacy and safety of monotherapy with one of the modern antidepressants (venlafaxine, agomelatine, or fluvoxamine) and combination treatment of one of the above mentioned antidepressants with acetyl-L-carnitine (ALС, carnicetine) in the geriatric psychiatric unit. Materials and methods. Two groups of elderly patients (aged 60—79 years) with mild or moderate depression, randomized according to a number of demographic and clinical characteristics, were treated with antidepressants in monotherapy or combined therapy (antidepressant/carnicetine) within 8 weeks. Results. Combination therapy with the neurotrophic agent carnicetine proved to be more effective compared to monotherapy. At the end of treatment, the more rapid clinical response has been shown for depression, anxiety, apathy, and cognitive dysfunction. Furthermore, combination therapy provides less adverse effects. Conclusion. Antidepressant/carnicetine combination therapy may be recommended for treatment of depression in elderly patients.